中国P站

Abstract

Therapeutic oligonucleotides bind via Watson-Crick hybridization to their molecular RNA targets that are known to be central for the pathomechanism of a disease, ultimately aiming at clinical improvement. Antisense oligonucleotides (ASO) and small interfering RNAs (siRNA) leading to RNA interference (RNAi) are amongst the two most widely used therapeutic oligonucleotides. One outstanding property of such oligonucleotides is the specificity of target binding which is much higher as compared to other drugs, commonly represented by small molecules or more recently by antibodies. The liver has evolved as a model target tissue where the concept of therapeutic oligonucleotides can be excellently evaluated. A significant number of genes involved in disease have been described for the liver that may allow therapeutic intervention by oligonucleotides. Transthyretin (TTR), a human serum protein expressed by the liver is the cause of familial amyloid polyneuropathy (FAP). Oligonucleotides directed against TTR mRNA are now under investigation in advanced clinical trials and attract major attention to the field, since the next clinical verification of the concept of therapeutic oligonucleotides seems to be close. This review will focus on recent advances in the ongoing clinical studies that involve ASO and siRNA directed against TTR.

Biography

Email: hepar@ukmuenster.de